TY  - JOUR
A1  - Michalik-Onichimowska, Aleksandra
A1  - Kern, Simon
A1  - Riedel, Jens
A1  - Panne, Ulrich
A1  - King, Rudibert
A1  - Maiwald, Michael
T1  - "Click" analytics for "click" chemistry - A simple method for calibration-free evaluation of online NMR spectra
JF  - Journal of magnetic resonance
N2  - Driven mostly by the search for chemical syntheses under biocompatible conditions, so called "click" chemistry rapidly became a growing field of research. The resulting simple one-pot reactions are so far only scarcely accompanied by an adequate optimization via comparably straightforward and robust analysis techniques possessing short set-up times. Here, we report on a fast and reliable calibration-free online NMR monitoring approach for technical mixtures. It combines a versatile fluidic system, continuous-flow measurement of H-1 spectra with a time interval of 20 s per spectrum, and a robust, fully automated algorithm to interpret the obtained data. As a proof-of-concept, the thiol-ene coupling between N-boc cysteine methyl ester and ally] alcohol was conducted in a variety of non-deuterated solvents while its time-resolved behaviour was characterized with step tracer experiments. Overlapping signals in online spectra during thiol-ene coupling could be deconvoluted with a spectral model using indirect hard modeling and were subsequently converted to either molar ratios (using a calibration free approach) or absolute concentrations (using 1-point calibration). For various solvents the kinetic constant k for pseudo-first order reaction was estimated to be 3.9 h(-1) at 25 degrees C. The obtained results were compared with direct integration of non-overlapping signals and showed good agreement with the implemented mass balance. (C) 2017 Elsevier Inc. All rights reserved.
KW  - NMR spectroscopy
KW  - Reaction monitoring
KW  - Automated data evaluation
KW  - Thiol-ene click chemistry
Y1  - 2017
U6  - https://doi.org/10.1016/j.jmr.2017.02.018
SN  - 1090-7807
SN  - 1096-0856
VL  - 277
SP  - 154
EP  - 161
PB  - Elsevier
CY  - San Diego
ER  -